Abstract
We tested the hypothesis that large areas of small hard drusen (diameter <63 µm) and intermediate drusen (diameter 63–124 µm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least two consecutive visits spaced five years apart over a 20-year period were included. A 6-level severity scale, including no drusen, four levels of increasing area (from minimal (<2596 µm²) to large (>9086 µm²)) of only small hard drusen, and intermediate drusen, was used. The five-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (p < 0.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p < 0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.
Highlights
Age-related macular degeneration (AMD) is a complex chronic disease affecting multiple layers of the retina
In the Beaver Dam Eye Study, we found that the incidence of increasingly larger areas of small hard drusen is dependent upon the prior less severe level of small hard drusen
This report provides long-term population-based observations regarding the relationships of age, sex, and presence of risk alleles for two age-related macular degeneration (AMD) candidate genes, CFH Y402H rs1061170 and ARMS2
Summary
Age-related macular degeneration (AMD) is a complex chronic disease affecting multiple layers of the retina. Its earliest subclinical stages have been defined by the presence of age-related thickening of Bruch membrane with calcifications and basal laminar deposits prior to the appearance of hard and soft drusen in the macula as detected by ophthalmoscopy [1]. Its earliest stages are often defined by the presence of large soft drusen (≥125 μm in diameter) [2,3]. Progression of AMD involves the appearance of increasing numbers of large soft distinct and indistinct drusen that may become confluent, as well as the development of pigmentary abnormalities (depigmentation and increased retinal pigment) of the retinal pigment epithelium (RPE) in the macula. Reduction in choroidal perfusion and retinal tissue oxygenation levels, increased systemic inflammation, presence of atherosclerosis, and elastic tissue degeneration have been hypothesized to be involved in the pathogenesis of AMD [3,4]. Genes associated with the alternative complement system, lipid metabolism, atherosclerosis, and other pathways have been found to be associated with the development of late AMD [5,6]
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